A longitudinal study on the effect of nifedipine therapy and its discontinuation on [Ca2+]i and proliferation of B lymphocytes of dialysis patients

The abnormalities in cytosolic calcium ([Ca2+]i) and proliferation of B cells in uremic patients are significantly improved by treatment with nifedipine. The rapidity with which this agent induces its beneficial effect and whether these derangements reemerge after cessation of therapy are not known. We studied six hemodialysis patients before, during, and after treatment with nifedipine. Before treatment, [Ca2+]i of B cells was markedly elevated (125 +/- 4.3 nmol/L) and their proliferation markedly reduced (5.2 +/- 0.36 x 10(3) cpm). After 1 month of therapy, [Ca2+]i fell significantly (P < 0.01) to 95 +/- 1.7 nmol/L and to a normal value of 84 +/- 1.6 after 2 months. The levels of [Ca2+]i rose significantly (P < 0.01) to 95 +/- 2.3 nmol/L after 1 month of cessation of therapy and were 115 +/- 2.8 nmol/L by 2 months, Proliferation of B cells improved significantly (P < 0.01) after 1 month of therapy (9.4 +/- 1.1 x 10(3) cpm) with further improvement during the subsequent month, reaching a normal value (12.2 +/- 1.1 x 10(3) cpm) by the end of the 2 months. Proliferation of B cells decreased after cessation of therapy and was 5.2 +/- 0.17 x 10(3) cpm after 2 months, a value similar to the pretreatment level. The blunted inhibitory effect of PTH-(1-84) on B cell proliferation was reversed by nifedipine treatment and reappeared after discontinuation of therapy. Also, serum globulin levels increased after administration of nifedipine and decreased again after cessation of treatment. The results show that nifedipine rapidly reversed the elevation in [Ca2+]i of B cells, the impairment in their proliferation, and the blunted inhibitory effect of PTH on B cell proliferation, and was associated with increased serum globulin levels, These derangements reemerged after cessation of therapy. These data indicate that nifedipine therapy is effective in the management of the abnormalities in B cell metabolism and function in hemodialysis patients. The treatment with this drug must be maintained to sustain its beneficial effects. Other calcium channel blockers may also be effective, but their effects were not examined in the current study. (C) 1997 by the National Kidney Foundation, Inc.